Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy

Tineke Vandenbroucke; Magali Verheecke; The International Network on Cancer, Infertility and Pregnancy (INCIP); Mathilde van Gerwen; Kristel Van Calsteren; Michael J. Halaska; Monica Fumagalli; Robert Fruscio; Amarendra Gandhi; Margreet Veening; Lieven Lagae; Petronella B. Ottevanger; Jens Uwe Voigt; Jorine de Haan; Mina M. Gziri; Charlotte Maggen; Luc Mertens; Gunnar Naulaers; Laurence Claes; Frédéric Amant

doi:10.1016/j.ejca.2020.07.004

Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy

Tineke Vandenbroucke, Magali Verheecke, The International Network on Cancer, Infertility and Pregnancy (INCIP), Mathilde van Gerwen, Kristel Van Calsteren, Michael J. Halaska, Monica Fumagalli, Robert Fruscio, Amarendra Gandhi, Margreet Veening, Lieven Lagae, Petronella B. Ottevanger, Jens Uwe Voigt, Jorine de Haan, Mina M. Gziri, Charlotte Maggen, Luc Mertens, Gunnar Naulaers, Laurence Claes, Frédéric Amant^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6–4.3, versus 4.5, 95% CI: 4.1–4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). Conclusions: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. Clinical trial registration: The study is registered at ClinicalTrials.gov, NCT00330447.

Original language	English
Pages (from-to)	57-67
Number of pages	11
Journal	European Journal of Cancer
Volume	138
DOIs	https://doi.org/10.1016/j.ejca.2020.07.004
Publication status	Published - Oct 2020

Bibliographical note

Funding Information:
This research was supported by European Union's Horizon 2020 research and innovation programme (No. 647047 ), Research Foundation-Flanders , Stichting tegen Kanker , Belgian Cancer Plan , Koningin Wilhelmina Fonds , Kom Op Tegen Kanker , Stichting Mitialto and Charles University grant PROGRES Q-34. The funding sources had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication.

Funding Information:
This research was supported by European Union's Horizon 2020 research and innovation programme (No. 647047), Research Foundation-Flanders, Stichting tegen Kanker, Belgian Cancer Plan, Koningin Wilhelmina Fonds, Kom Op Tegen Kanker, Stichting Mitialto and Charles University grant PROGRES Q-34. The funding sources had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication.

Publisher Copyright:
© 2020 The Author(s)

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Vandenbroucke, T., Verheecke, M., The International Network on Cancer, Infertility and Pregnancy (INCIP), van Gerwen, M., Van Calsteren, K., Halaska, M. J., Fumagalli, M., Fruscio, R., Gandhi, A., Veening, M., Lagae, L., Ottevanger, P. B., Voigt, J. U., de Haan, J., Gziri, M. M., Maggen, C., Mertens, L., Naulaers, G., Claes, L., & Amant, F. (2020). Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy. European Journal of Cancer, 138, 57-67. https://doi.org/10.1016/j.ejca.2020.07.004

@article{2f1dc8fa3e8242f6aaeed61fb9e249b4,

title = "Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy",

abstract = "Background: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6–4.3, versus 4.5, 95% CI: 4.1–4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). Conclusions: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. Clinical trial registration: The study is registered at ClinicalTrials.gov, NCT00330447.",

author = "Tineke Vandenbroucke and Magali Verheecke and {The International Network on Cancer, Infertility and Pregnancy (INCIP)} and {van Gerwen}, Mathilde and {Van Calsteren}, Kristel and Halaska, {Michael J.} and Monica Fumagalli and Robert Fruscio and Amarendra Gandhi and Margreet Veening and Lieven Lagae and Ottevanger, {Petronella B.} and Voigt, {Jens Uwe} and {de Haan}, Jorine and Gziri, {Mina M.} and Charlotte Maggen and Luc Mertens and Gunnar Naulaers and Laurence Claes and Fr{\'e}d{\'e}ric Amant and Jeroen Blommaert and Jana Dekrem and Frederic Goffin and Vincent Rigo and Camilla Fontana and Fabio Mosca and Sofia Passera and Odoardo Picciolini and Giovanna Scarfone and Peccatori, {Fedro Alessandro} and Boffi, {Maria Lucia} and {Delle Marchette}, Martina and Renata Nacinovich and Christianne Lok and Vera Wolters and Ingrid Boere and Els Witteveen and Carolina Schr{\"o}der and {de Groot}, Christianne and {van Grotel}, Martine and {van den Heuvel-Eibrink}, Marry and Anna Babkova and V{\'i}t Droch{\'y}tek",

note = "Funding Information: This research was supported by European Union's Horizon 2020 research and innovation programme (No. 647047 ), Research Foundation-Flanders , Stichting tegen Kanker , Belgian Cancer Plan , Koningin Wilhelmina Fonds , Kom Op Tegen Kanker , Stichting Mitialto and Charles University grant PROGRES Q-34. The funding sources had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication. Funding Information: This research was supported by European Union's Horizon 2020 research and innovation programme (No. 647047), Research Foundation-Flanders, Stichting tegen Kanker, Belgian Cancer Plan, Koningin Wilhelmina Fonds, Kom Op Tegen Kanker, Stichting Mitialto and Charles University grant PROGRES Q-34. The funding sources had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = oct,

doi = "10.1016/j.ejca.2020.07.004",

language = "English",

volume = "138",

pages = "57--67",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd.",

}

Vandenbroucke, T, Verheecke, M, The International Network on Cancer, Infertility and Pregnancy (INCIP), van Gerwen, M, Van Calsteren, K, Halaska, MJ, Fumagalli, M, Fruscio, R, Gandhi, A, Veening, M, Lagae, L, Ottevanger, PB, Voigt, JU, de Haan, J, Gziri, MM, Maggen, C, Mertens, L, Naulaers, G, Claes, L & Amant, F 2020, 'Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy', European Journal of Cancer, vol. 138, pp. 57-67. https://doi.org/10.1016/j.ejca.2020.07.004

TY - JOUR

T1 - Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy

AU - Vandenbroucke, Tineke

AU - Verheecke, Magali

AU - The International Network on Cancer, Infertility and Pregnancy (INCIP)

AU - van Gerwen, Mathilde

AU - Van Calsteren, Kristel

AU - Halaska, Michael J.

AU - Fumagalli, Monica

AU - Fruscio, Robert

AU - Gandhi, Amarendra

AU - Veening, Margreet

AU - Lagae, Lieven

AU - Ottevanger, Petronella B.

AU - Voigt, Jens Uwe

AU - de Haan, Jorine

AU - Gziri, Mina M.

AU - Maggen, Charlotte

AU - Mertens, Luc

AU - Naulaers, Gunnar

AU - Claes, Laurence

AU - Amant, Frédéric

AU - Blommaert, Jeroen

AU - Dekrem, Jana

AU - Goffin, Frederic

AU - Rigo, Vincent

AU - Fontana, Camilla

AU - Mosca, Fabio

AU - Passera, Sofia

AU - Picciolini, Odoardo

AU - Scarfone, Giovanna

AU - Peccatori, Fedro Alessandro

AU - Boffi, Maria Lucia

AU - Delle Marchette, Martina

AU - Nacinovich, Renata

AU - Lok, Christianne

AU - Wolters, Vera

AU - Boere, Ingrid

AU - Witteveen, Els

AU - Schröder, Carolina

AU - de Groot, Christianne

AU - van Grotel, Martine

AU - van den Heuvel-Eibrink, Marry

AU - Babkova, Anna

AU - Drochýtek, Vít

N1 - Funding Information: This research was supported by European Union's Horizon 2020 research and innovation programme (No. 647047 ), Research Foundation-Flanders , Stichting tegen Kanker , Belgian Cancer Plan , Koningin Wilhelmina Fonds , Kom Op Tegen Kanker , Stichting Mitialto and Charles University grant PROGRES Q-34. The funding sources had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication. Funding Information: This research was supported by European Union's Horizon 2020 research and innovation programme (No. 647047), Research Foundation-Flanders, Stichting tegen Kanker, Belgian Cancer Plan, Koningin Wilhelmina Fonds, Kom Op Tegen Kanker, Stichting Mitialto and Charles University grant PROGRES Q-34. The funding sources had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication. Publisher Copyright: © 2020 The Author(s)

PY - 2020/10

Y1 - 2020/10

N2 - Background: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6–4.3, versus 4.5, 95% CI: 4.1–4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). Conclusions: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. Clinical trial registration: The study is registered at ClinicalTrials.gov, NCT00330447.

AB - Background: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6–4.3, versus 4.5, 95% CI: 4.1–4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). Conclusions: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. Clinical trial registration: The study is registered at ClinicalTrials.gov, NCT00330447.

UR - http://www.scopus.com/inward/record.url?scp=85089819452&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2020.07.004

DO - 10.1016/j.ejca.2020.07.004

M3 - Article

C2 - 32858478

AN - SCOPUS:85089819452

SN - 0959-8049

VL - 138

SP - 57

EP - 67

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy

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